NMPA Approves Lupeng’s Rocbrutinib, China’s First Fourth-Generation BTK Inhibitor

Lupeng Pharmaceutical announced that China’s National Medical Products Administration (NMPA) has granted accelerated approval to its fourth-generation BTK inhibitor, Rocbrutinib (LP-168). The approval covers adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL) who have received at least two prior systemic therapies, including BTK inhibitors. The approval makes Rocbrutinib the first fourth-generation BTK inhibitor approved in China and provides a new treatment option for patients with heavily pretreated R/R MCL.

Clinical Evidence from ROCK-1

The approval was supported by data from the Phase II ROCK-1 study (NCT05716087), conducted across 41 centers in China. Rocbrutinib achieved an objective response rate (ORR) of 63.9%, with a complete response (CR) rate of 23%. Median duration of response (mDOR) reached 16.5 months. Rocbrutinib demonstrated a manageable safety profile, with no reported atrial fibrillation or major cardiac events and no treatment discontinuations due to adverse reactions. All enrolled patients had prior exposure to covalent BTK inhibitors, and more than one-third had received two or more BTK-targeted therapies.

Breakthrough Therapy Designation and Guideline Inclusion

In May 2024, Rocbrutinib was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) for adult patients with non-GCB diffuse large B-cell lymphoma (DLBCL) after at least two prior lines of therapy. Reflecting its growing clinical relevance, Rocbrutinib was included in the Chinese Society of Clinical Oncology (CSCO) Lymphoma Guidelines in April 2026 as a Category II recommendation for R/R MCL.

Mechanism of Action

Rocbrutinib is designed to overcome resistance mutations associated with earlier-generation BTK inhibitors. By combining covalent and non-covalent binding mechanisms, the drug targets multiple resistance mutations, including C481, T474I, and L528W, broadening its therapeutic potential in heavily pretreated patients.

Global Development Program

In addition to its approval in China, Rocbrutinib is being evaluated globally across multiple B-cell malignancies. Results from a Phase I study (NCT04775745) in the United States demonstrated an ORR of 78.3% in CLL patients previously treated with BTK inhibitors at doses of 200–300 mg/day, with a median progression-free survival (PFS) of 28.1 months in the 100–300 mg/day range. In January 2026, Lupeng launched the ROCKET-CLL Phase III trial (NCT07342478), a head-to-head comparison of Rocbrutinib versus the third-generation non-covalent BTK inhibitor pirtobrutinib in relapsed or refractory CLL/SLL.

Additional programs include the ROCK-2 Phase II study (NCT07189065) in non-GCB DLBCL and a global Phase III trial in R/R CLL/SLL.

Expert Perspectives

Chinese lymphoma experts highlighted Rocbrutinib’s potential to address a significant unmet need in R/R MCL, particularly for patients who have exhausted prior BTK-targeted treatment options.

They noted that the drug’s clinical activity and safety profile support its emergence as an important treatment option in this challenging disease setting.

Pipeline Expansion and Innovation Platform

Beyond mantle cell lymphoma, Rocbrutinib is under investigation for other B-cell malignancies, including DLBCL, CLL/SLL, and marginal zone lymphoma (MZL).

Dr. Chen Yi, co-founder and CSO of Lupeng Pharmaceutical, highlighted that Rocbrutinib’s market launch exemplifies the company’s “innovation methodology,” leveraging its proprietary BeyondX Oral MedChem Platform to efficiently develop next-generation, best-in-class small molecule targeted therapies.

The approval marks an important milestone for Lupeng Pharmaceutical as it advances its next-generation BTK inhibitor program globally.

Reference

Lupeng Pharmaceutical’s Fourth-Generation BTK Inhibitor Rocbrutinib Approved in China for Relapsed or Refractory Mantle Cell Lymphoma